3S9D: Binary Complex Between Ifna2 And Ifnar2

Citation:
Abstract
Type I Interferons (IFNs) are important cytokines for innate immunity against viruses and cancer. Sixteen human type I IFN variants signal through the same cell-surface receptors, IFNAR1 and IFNAR2, yet they can evoke markedly different physiological effects. The crystal structures of two human type I IFN ternary signaling complexes containing IFNalpha2 and IFNomega reveal recognition modes and heterotrimeric architectures that are unique among the cytokine receptor superfamily but conserved between different type I IFNs. Receptor-ligand cross-reactivity is enabled by conserved receptor-ligand "anchor points" interspersed among ligand-specific interactions that "tune" the relative IFN-binding affinities, in an apparent extracellular "ligand proofreading" mechanism that modulates biological activity. Functional differences between IFNs are linked to their respective receptor recognition chemistries, in concert with a ligand-induced conformational change in IFNAR1, that collectively control signal initiation and complex stability, ultimately regulating differential STAT phosphorylation profiles, receptor internalization rates, and downstream gene expression patterns.
PDB ID: 3S9DDownload
MMDB ID: 93330
PDB Deposition Date: 2011/6/1
Updated in MMDB: 2011/09
Experimental Method:
x-ray diffraction
Resolution: 2  Å
Source Organism:
Similar Structures:
Biological Unit for 3S9D: dimeric; determined by author and by software (PISA)
Molecular Components in 3S9D
Label Count Molecule
Proteins (2 molecules)
1
Interferon Alpha-2(Gene symbol: IFNA2)
Molecule annotation
1
Interferon Alpha/beta Receptor 2(Gene symbol: IFNAR2)
Molecule annotation
* Click molecule labels to explore molecular sequence information.

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